Treatment of Preeclampsia Symptoms through Modulation of Bcl-2 and Beclin-1 Homeostasis Using Kopyor Coconut Water
Fitriana Fitriana 1, 5, Sri Sulistyowati 1, 2*, Dono Indarto 1, 3 , Soetrisno Soetrisno 1, 4
Journal of Angiotherapy 8(5) 1-9 https://doi.org/10.25163/angiotherapy.859683
Submitted: 28 March 2024 Revised: 20 May 2024 Published: 21 May 2024
Kopyor Coconut Water showed potential in reducing preeclampsia symptoms by modulating autophagy and apoptosis, suggesting therapeutic benefits.
Abstract
Background: Preeclampsia (PE) is a significant contributor to maternal and perinatal morbidity and mortality, especially in low-income countries. The condition, characterized by hypertension and proteinuria after 20 weeks of gestation, has complex and poorly understood pathophysiological mechanisms, primarily involving placental dysfunction. Recent studies suggest that autophagy and apoptosis play crucial roles in PE progression. This study investigates the potential therapeutic effects of Kopyor coconut water (KCW) on PE, focusing on its mineral content and impact on placental autophagy and apoptosis. Methods: Female Wistar rats were induced with PE using L-NAME, a nitric oxide synthase inhibitor, and divided into five groups, including controls and treatments with low-dose aspirin (LDA) and KCW. The mineral content of KCW was analyzed using Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES). Placental levels of Beclin-1 and Bcl-2 were measured to assess autophagy and apoptosis. Blood pressure and proteinuria were monitored, and pregnancy outcomes were evaluated. Results: KCW contained significant levels of potassium, calcium, sodium, magnesium, and phosphorus, essential for cellular functions and homeostasis. In L-NAME-induced PE rats, KCW and LDA treatments significantly reduced systolic blood pressure and proteinuria. Placental analysis showed that KCW treatment increased Beclin-1 levels and decreased Bcl-2 levels, indicating enhanced autophagy and reduced apoptosis. Additionally, KCW improved pregnancy outcomes, including the number of live fetuses, without significantly affecting placental weight. Conclusion: KCW's mineral-rich composition effectively modulates placental autophagy and apoptosis, reducing PE symptoms and improving pregnancy outcomes in L-NAME-induced PE rats. These findings suggest that KCW could be a promising nutritional therapy for managing and preventing PE, warranting further research in human studies.
Keywords: Preeclampsia, Preeclampsia, Kopyor Coconut Water, Autophagy, Apoptosis, L-NAME, Bcl-2, Beclin-1, Proteinuria
References
ACOG. (2020). The American College of Obstetricians and Gynecologists, 2020.Gestational Hypertension and Preeclampsia: ACOG Practice Bulletin Summary, Number 222. Obstetrics and Gynecology, 135(6), 1492–1495.
Bhagya, D., Prema, L., & Rajamohan, T. (2012). Therapeutic effects of tender coconut water on oxidative stress in fructose fed insulin resistant hypertensive rats. Asian Pacific Journal of Tropical Medicine, 5(4), 270–276. https://doi.org/10.1016/S1995-7645(12)60038-8
Bouter, A. R., & Duvekot, J. J. (2020). Evaluation of the clinical impact of the revised ISSHP and ACOG definitions on preeclampsia. Pregnancy Hypertension.
Chaemsaithong, P., Sahota, D. S., & Poon, L. C. (2020). First trimester preeclampsia screening and prediction. American Journal of Obstetrics and Gynecology. https://doi.org/10.1016/j.ajog.2020.07.020
Cora, M. C., Kooistra, L., & Travlos, G. (2015). Vaginal Cytology of the Laboratory Rat and Mouse:Review and Criteria for the Staging of the Estrous Cycle Using Stained Vaginal Smears. Toxicologic Pathology, 43(6), 776–793. https://doi.org/10.1177/0192623315570339
Cornelius, D. C., & Wallace, K. (2020). Autophagy in preeclampsia: A new target? EBioMedicine, 57, 0–1. https://doi.org/10.1016/j.ebiom.2020.102864
Cragg, G. M., & Pezzuto, J. M. (2016). Natural Products as a Vital Source for the Discovery of Cancer Chemotherapeutic and Chemopreventive Agents. Medical Principles and Practice, 25(2), 41–59. https://doi.org/10.1159/000443404
Franzoni, F., Santoro, G., Carpi, A., Da Prato, F., Bartolomucci, F., Femia, F. R., Prattichizzo, F., & Galetta, F. (2005). Antihypertensive effect of oral potassium aspartate supplementation in mild to moderate arterial hypertension. Biomedicine and Pharmacotherapy, 59(1–2), 25–29. https://doi.org/10.1016/j.biopha.2004.11.002
Gatford, K. L., Andraweera, P. H., Roberts, C. T., & Care, A. S. (2020). Animal Models of Preeclampsia: Causes, Consequences, and Interventions. Hypertension, 75(6), 1363–1381. https://doi.org/10.1161/HYPERTENSIONAHA.119.14598
Golyanovskyi, V. (2021). Combined prevention of fetal growth restriction based on determination of diagnostic markers. In EUREKA: Health Sciences. journal.eu-jr.eu.
Gong, J. S., & Kim, G. J. (2014). The role of autophagy in the placenta as a regulator of cell death. Clinical and Experimental Reproductive Medicine, 41(3), 97–107. https://doi.org/10.5653/cerm.2014.41.3.97
Guo, K. M., Li, W., Wang, Z. H., He, L. C., Feng, Y., & Liu, H. S. (2022). Low-dose aspirin inhibits trophoblast cell apoptosis by activating the CREB/Bcl-2 pathway in pre-eclampsia. Cell Cycle, 21(21), 2223–2238. https://doi.org/10.1080/15384101.2022.2092814
Hofmeyr, G. J., Lawrie, T. A., Atallah, Á. N., & Torloni, M. R. (2018). Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database of Systematic Reviews, 2018(10). https://doi.org/10.1002/14651858.CD001059.pub5
Houston, M. (2011). The role of magnesium in hypertension and cardiovascular disease. Journal of Clinical Hypertension, 13(11), 843–847. https://doi.org/10.1111/j.1751-7176.2011.00538.x
Karimi, Z., Alizadeh, A. M., Dolatabadi, J. E. N., & Dehghan, P. (2019). Nigella sativa and its derivatives as food toxicity protectant agents. Advanced Pharmaceutical Bulletin, 9(1), 22–37. https://doi.org/10.15171/apb.2019.004
Korokin, M., Gureev, V., Gudyrev, O., Golubev, I., Korokina, L., Peresypkina, A., Pokrovskaia, T., Lazareva, G., Soldatov, V., Zatolokina, M., Pobeda, A., Avdeeva, E., Beskhmelnitsyna, E., Denisyuk, T., Avdeeva, N., Bushueva, O., & Pokrovskii, M. (2020). Erythropoietin mimetic peptide (pHBSP) corrects endothelial dysfunction in a rat model of preeclampsia. International Journal of Molecular Sciences, 21(18), 1–20. https://doi.org/10.3390/ijms21186759
Lakshmanan, J., Zhang, B., Wright, K., Motameni, A. T., Jaganathan, V. L., Schultz, D. J., Klinge, C. M., & Harbrecht, B. G. (2020). Tender coconut water suppresses hepatic inflammation by activating AKT and JNK signaling pathways in an in vitro model of sepsis. Journal of Functional Foods, 64(October 2019), 103637. https://doi.org/10.1016/j.jff.2019.103637
Liu, C., Ji, L., Hu, J., Zhao, Y., Johnston, L. J., Zhang, X., & Ma, X. (2021). Functional amino acids and autophagy: Diverse signal transduction and application. International Journal of Molecular Sciences, 22(21). https://doi.org/10.3390/ijms222111427
Liu, Y., Wang, X., Fu, W., Cao, Y., Dou, W., Duan, D., Zhao, X., Ma, S., & Lyu, Q. (2023). The association between dietary mineral intake and the risk of preeclampsia in Chinese pregnant women?: a matched case – control study. Scientific Reports, 1–9. https://doi.org/10.1038/s41598-023-43481-4
Manivannan, A., Bhardwaj, R., Padmanabhan, S., Suneja, P., Hebbar, K. B., & Kanade, S. R. (2018). Biochemical and nutritional characterization of coconut (Cocos nucifera L.) haustorium. In Food Chemistry (Vol. 238). https://doi.org/10.1016/j.foodchem.2016.10.127
Marquez, R. T., & Xu, L. (2012). Bcl-2:Beclin 1 complex: multiple, mechanisms regulating autophagy/apoptosis toggle switch. American Journal of Cancer Research, 2(2), 214–221.
Nakashima, A., Shima, T., Tsuda, S., Aoki, A., & ... (2020). Disruption of placental homeostasis leads to preeclampsia. International Journal of ….
Prades, A., Dornier, M., Diop, N., & Pain, J. P. (2012). Coconut water uses, composition and properties: A review. Fruits, 67(2), 87–107. https://doi.org/10.1051/fruits/2012002
Prathapan, A., & Rajamohan, T. (2011). Antioxidant and antithrombotic activity of tender coconut water in experimental myocardial infarction. Journal of Food Biochemistry, 35(5), 1501–1507. https://doi.org/10.1111/j.1745-4514.2010.00471.x
Rahma, H., Indrawan, I. W. A., Nooryanto, M., Rahajeng, & Keman, K. (2017). Effect of a black cumin (Nigella sativa) ethanol extract on placental angiotensin II type 1-receptor autoantibody (AT1-AA) serum levels and endothelin-1 (ET-1) expression in a preeclampsia mouse model. Journal of Taibah University Medical Sciences. https://doi.org/10.1016/j.jtumed.2017.06.002
Rana, S., Lemoine, E., Granger, J., & Karumanchi, S. A. (2019). Preeclampsia: Pathophysiology, Challenges, and Perspectives. Circulation Research, 124(7), 1094–1112. https://doi.org/10.1161/CIRCRESAHA.118.313276
Rao, S. S., & Najam, R. (2016). Coconut water of different maturity stages ameliorates inflamatory processes in model of inflammation. Journal of Intercultural Ethnopharmacology, 5(3), 244–249. https://doi.org/10.5455/jice.20160402120142
Raoofi, A., Rostamzadeh, A., Ahmadi, R., & ... (2020). Effects of nitric oxide on reproductive organs and related physiological processes. Asian Pacific Journal ….
Rezeck Nunes, P., Gustavo de Oliveira, L., Romão Veiga, M., & Terezinha Serrão Peraçoli, M. (2019). Autophagy in Preeclampsia. Prediction of Maternal and Fetal Syndrome of Preeclampsia, 1–16. https://doi.org/10.5772/intechopen.85592
Schiffer, V., Evers, L., de Haas, S., Doha-Ghossein, C., Al-Nasiryp, S., & Spaanderman, M. (2018). 153. Spiral arterial blood flow during pregnancy; a systematic review and meta-analysis. Pregnancy Hypertension, 13, S87. https://doi.org/10.1016/j.preghy.2018.08.257
Wan, R., Yao, P., Wang, Y., Zhang, L., Guo, W., Du, M., Wang, Y., Shi, W., & Li, W. (2024). Autophagy-related biomarkers in preeclampsia: the underlying mechanism, correlation to the immune microenvironment and drug screening. BMC Pregnancy and Childbirth, 24(1), 1–15. https://doi.org/10.1186/s12884-023-06211-2
Wu, H., Huang, S., & Zhang, D. (2015). Autophagic responses to hypoxia and anticancer therapy in head and neck cancer. Pathology Research and Practice, 211(2), 101–108. https://doi.org/10.1016/j.prp.2014.11.010
Xu, H., & Qin, Z. (2020). Beclin 1, Bcl-2 and Autophagy (Issue July). Springer Singapore. https://doi.org/10.1007/978-981-15-0602-4
Zarean, E., & Tarjan, A. (2017). Effect of Magnesium Supplement on Pregnancy Outcomes: A Randomized Control Trial. Advanced Biomedical Research, 6(1), 109. https://doi.org/10.4103/2277-9175.213879
Zhang, L., Zhang, H., Ma, J., Wang, Y., Pei, Z., & Ding, H. (2022). Effects of thymoquinone against angiotensin II-induced cardiac damage in apolipoprotein E-deficient mice. International Journal of Molecular Medicine, 49(5), 1–12. https://doi.org/10.3892/IJMM.2022.5119
Zhao, Z., Yu, S., Li, M., Gui, X., & Li, P. (2018). Isolation of Exosome-Like Nanoparticles and Analysis of MicroRNAs Derived from Coconut Water Based on Small RNA High-Throughput Sequencing. Journal of Agricultural and Food Chemistry, 66(11), 2749–2757. https://doi.org/10.1021/acs.jafc.7b05614
Zulaikhah, S. T. (2019). Health Benefits of Tender Coconut Water (TCW). International Journal of Pharmaceutical Sciences and Research, 10(2), 474–480. https://doi.org/10.13040/IJPSR.0975-8232.10(2).474-80
View Dimensions
View Altmetric
Save
Citation
View
Share